内科学
餐后
内分泌学
胰高血糖素
肠促胰岛素
2型糖尿病
医学
胰岛素
胰高血糖素样肽-1
糖尿病
2型糖尿病
敌手
作者
Sofie Hædersdal,Asger Lund,Henrik Maagensen,Elisabeth Nielsen-Hannerup,Lærke S Gasbjerg,Mette M Rosenkilde,Julie Lyng Forman,Gerrit van Hall,Jens J Holst,Filip K Knop,Tina Vilsbøll
出处
期刊:European journal of endocrinology
[Bioscientifica]
日期:2021-12-01
摘要
Type 2 diabetes (T2D) pathophysiology includes fasting and postprandial hyperglucagonemia, which has been linked to hyperglycemia via increased endogenous glucose production (EGP). We used a glucagon receptor antagonist (LY2409021) and stable isotope tracer infusions to investigate consequences of hyperglucagonemia in type 2 diabetes.A double-blinded, randomized, placebo-controlled crossover study was conducted.Ten patients with T2D and ten matched non-diabetic controls underwent two liquid mixed meal tests preceded by single-dose administration of LY2409021 (100 mg) or placebo. Double-tracer technique was used to quantify EGP. Antagonist selectivity towards related incretin receptors was determined in vitro.Compared to placebo, LY2409021 lowered fasting plasma glucose from 9.1 to 7.1 mmol/L in patients and from 5.6 to 5.0 mmol/L in controls (both P<0.001) by mechanisms involving reduction of EGP. Postprandial plasma glucose excursions (baseline-subtracted area under the curve) were unaffected by LY2409021 in patients and increased in controls compared to placebo. Glucagon concentrations more than doubled during glucagon receptor antagonism. The antagonist interfered with both glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptors, complicating the interpretation of the postprandial data.LY2409021 lowered fasting plasma glucose concentrations but did not improve postprandial glucose tolerance after a meal in patients with T2D and controls. The metabolic consequences of postprandial hyperglucagonemia are difficult to evaluate using LY2409021 because of its antagonizing effects on the incretin receptors.
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